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Breast cancer survivors are living longer due to more effective therapies, but this means they are also at risk of long-term toxicities from cancer treatments, warned authors of a review in .

"Many cancer drugs affect the cardiovascular system with a range of clinical manifestations," said Lisa Carey, MD, ScM, of the University of North Carolina at Chapel Hill Lineberger Comprehensive Cancer Center, and colleagues. "Prompt diagnosis and treatment as well as a multidisciplinary approach involving a cardio-oncologist is optimal for management of these cardiovascular events."

Carey, who is deputy director of Clinical Sciences, discussed these issues in the following interview.

How common are treatment-related cardiovascular events in breast cancer survivors?

Carey: The incidence of treatment-related cardiovascular events in breast cancer survivors depends on characteristics such as the patient's age, the presence of cardiovascular risk factors or disease, the type of oncological drug received, and the length of therapies and available follow-up.

A recent examined cardiovascular risk in breast cancer survivors. It reported an increased relative risk of 20% for heart failure within the first year of diagnosis that persisted for at least 10 years thereafter. The pooled incidence rates of heart failure, coronary artery disease, and myocardial infarction were 4.44, 4.29, and 1.98 per 1,000 person-years. Adequate surveillance is needed because of the long survival achieved with novel therapies.

You mentioned that adverse cardiac events in real-world settings can be higher than reported in clinical trials, as evidenced by with CDK4-6i treatment. What did this study find?

Carey: A total of 266 patients with breast cancer and receiving CDK4-6 inhibitors were retrospectively studied to evaluate the incidence of thrombosis. Thrombosis during treatment, or within 30 days of CDK inhibitor discontinuation, were considered related to CDK4-6. More than 80% of patients received palbociclib, and 10% of the population had thrombotic events. The 1-year incidence of thrombosis was 10.9%, 8.3%, and 4.8% on palbociclib, ribociclib, and abemaciclib, respectively. The Khorana Risk Score for Venous Thromboembolism, used in clinical practice, did not help predict this risk. Larger studies are needed.

What do you advise for assessing cardiovascular risk pre-treatment in patients with breast cancer?

Carey: As reported in our review, it is important to recognize, treat, and control preexisting cardiovascular risk factors before initiating cardiotoxic drugs, taking into account the risk of cardiovascular toxicity related to the drug that the patient should receive. It is helpful to inform and advise patients to promote a healthy lifestyle -- i.e., stop smoking, be physically active, maintain an adequate BMI [body mass index], control lipid profile and glycemia, etc.

The 2022 European Society of Cardiology have important and helpful recommendations, including a cardiovascular toxicity risk assessment (during the first year after cardiotoxic cancer treatment) with risk stratification for surveillance, and primary/secondary prevention strategies of cancer therapy-related cardiovascular toxicity.

What do you advise about monitoring patients for adverse cardiac events?

Carey: Oncologists need to be aware of the manifestations of adverse cardiac events, recognizing the specific cardiac toxicity related to the oncological drug/treatment the patient is receiving.

On some therapies, the use of echo-ultrasound for monitoring adverse cardiac events is recommended (like trastuzumab). For other treatments, clinical and physical monitoring and attention for cardiovascular-related signs and symptoms is needed.

If there is doubt, strategies to exclude cardiac events should be performed with biochemical and radiological assessment. With a clinical suspicion of cardiac toxicity, it is important to require a multidisciplinary team discussion between oncologists and cardiologists to better understand diagnosis, treatment, and management of cardiac events and oncological drugs.

What do you advise about managing these events when they manifest, and can you give an example?

Carey: As previously mentioned, a multidisciplinary team discussion with oncologists and cardiologists -- or, if present, with a cardio-oncologist -- is needed in light of a suspected clinical manifestation of cardiovascular adverse events. Again, the 2022 European Society of Cardiology published recommendations based on the type of oncological treatment as well as the severity of the adverse event.

Cardiac serum biomarkers and cardiac imaging should be performed to address the type and diagnosis of cardiovascular events and the severity. The patient should be referred to a cardio-oncologist (or cardiologist) to tailor the management based on the clinical manifestation of cardiovascular events. Each drug can manifest cardiovascular events in a different way with specific management.

Multidisciplinary discussion is needed not only for the acute management but also in the follow-up and in the decision-making about the temporary or permanent discontinuation and the timing to restart the drug.

One example could be the manifestation of myocarditis during immunotherapy, if there is a suspicion of myocarditis because a patient complains of dyspnea and chest pain. Troponin and proBNP [pro b-type natriuretic peptide] along with ECG, echo-ultrasound, and cardiac MRI should be promptly performed. Moreover, the patient should interrupt immunotherapy and be referred to a cardiologist.

If the suspicion of immune-related myocarditis is supported by biomarkers and cardiac imaging, a high dose of corticosteroids should be started, with close monitoring of cardiac function. If the patient is steroid-refractory, other immunosuppressive drugs (e.g., alemtuzumab or abatacept, or with caution, the use of infliximab if heart failure) may be needed.

If the adverse events are resolved, attention and deep discussion are needed to evaluate the risk and benefit and the severity of the event, to decide the appropriate management of the systemic drug.

Read the study here and expert commentary about it here.